A 27-year-old woman with multiple sclerosis comes to the physician because of right arm numbness and mild balance problems for the past one month. She was diagnosed with multiple sclerosis one year ago after presenting with partial right-sided vision loss and finger tingling. She was treated with corticosteroids for two weeks and had improvement of her symptoms. She has been treated with glatiramer acetate since then. She developed a recurrence of right-sided hand numbness 1 month ago that progressed to right arm numbness and left leg weakness. Her past medical history is otherwise unremarkable.
Routine laboratory tests, including complete blood count and comprehensive metabolic panel, are unremarkable. Repeat MRI of the brain shows white matter changes that appear to be worse compared to the study one year ago. She is being considered for a switch to natalizumab therapy due to progressive disease.
Which of the following antibody titers would be most helpful in managing this patient?

Question

A 27-year-old woman with multiple sclerosis comes to the physician because of right arm numbness and mild balance problems for the past one month.  She was diagnosed with multiple sclerosis one year ago after presenting with partial right-sided vision loss and finger tingling.  She was treated with corticosteroids for two weeks and had improvement of her symptoms.  She has been treated with glatiramer acetate since then.  She developed a recurrence of right-sided hand numbness 1 month ago that progressed to right arm numbness and left leg weakness.  Her past medical history is otherwise unremarkable.
Routine laboratory tests, including complete blood count and comprehensive metabolic panel, are unremarkable.  Repeat MRI of the brain shows white matter changes that appear to be worse compared to the study one year ago.  She is being considered for a switch to natalizumab therapy due to progressive disease.
Which of the following antibody titers would be most helpful in managing this patient?

Quizplus · Accepted Answer

11ec193a_987b_a4b6_853d_53008dbaf050_MD0002_00 This patient presents with relapsing-remitting multiple sclerosis (RRMS), defined as disease relapse after full or partial recovery of initial MS symptoms. Acute MS attacks or relapses are initially treated with glucocorticoids, but immunomodulatory agents (e.g., interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab, and fingolimod) are continued indefinitely to decrease relapse rate and slow accumulation of lesions on MRI. Current guidelines recommend disease modifying therapy in all patients with RRMS using interferons or glatiramer as first-line therapy based on side-effect profile and clinical data. Patients developing side effects or having inadequate response to first-line agents may be switched to natalizumab, a recombinant monoclonal antibody against alpha-4 integrins that prevents adhesion of inflammatory lymphocytes and monocytes to vascular endothelium. However, the drug has been associated with the development of progressive multifocal leukoencephalopathy (PML), a fatal disease caused by JC virus reactivation. All patients should have JC virus antibody testing prior to starting natalizumab. Patients positive for JC virus antibodies are recommended to take fingolimod, which blocks lymphocyte migration from lymph nodes to the brain and prevents further inflammation. This drug is approved as a first-line agent, but is usually recommended as second-line due to the increased risk of infection and malignancy. (Choice A) BK virus infection is associated with tubulointerstitial nephritis and ureteral stenosis, primarily in renal transplant patients. (Choice B) Epstein-Barr virus (EBV) infection, particularly symptomatic mononucleosis, has been associated with a 2-3 fold increased risk of developing MS. However, EBV status does not affect the initiation of treatment with natalizumab. (Choice C) Patients receiving fingolimod have an increased rate of severe herpes simplex virus (HSV) infections, but previous HSV does not affect the initiation of treatment with natalizumab. (Choice E) Varicella zoster has been linked as a possible viral etiology for MS, but requires further studies. However, natalizumab is not associated with increased frequency of varicella infections. Educational objective: Natalizumab is a recombinant monoclonal antibody against alpha-4 integrins that is a second-line agent for relapsing-remitting multiple sclerosis. However, the drug has been associated with development of progressive multifocal leukoencephalopathy, and all patients should have JC virus antibody testing prior to starting natalizumab. __________ References: Natalizumab for relapsing remitting multiple sclerosis (http://www.ncbi.nlm.nih.gov/pubmed/21975773) Fingolimod in multiple sclerosis: Mechanisms of action and clinical efficacy (http://www.ncbi.nlm.nih.gov/pubmed/21669553)

A 27-Year-Old Woman with Multiple Sclerosis Comes to the Physician